12 – Miscellaneous Antimicrobials

Question 1

Metronidazole (Nitroimidazole Class): formulations

Answer 1

• Eradia oral suspension (NEW)
  o Treatment of Giardia duodenalis infection in dogs
  o Not licensed for bacterial infections
• Human products
  o Oral tablet
  o Injectable solution
  o Topical cream

Question 2

Metronidazole: mechanism

Answer 2

• Intracellular ANAEROBIC metabolism of drugs produces REACTIVE metabolites leading to DNA damage

Question 3

**Metronidazole: spectrum of activity

Answer 3

• ANAEROBES (Clostridium, Bacteroides, Brachyspira)
• Protozoa
• (Maybe Helicobacter, Camplyobacter: HUMAN)
• Limited activity against aerobic bacteria
• *good first choice if suspecting an anaerobic infection

Question 4

Metronidazole: resistance

Answer 4

• rare, but can occur with decreased intracellular drug activation
• cross-resistance between nitroimidazoles

Question 5

Metronidazole: PK

Answer 5

• generally good oral bioavailability
• volume of distribution, 1L/kg, penetrates many tissues (bit better than beta-lactams)
• elimination
  o hepatic metabolism
  o elimination in bile and urine

Question 6

*Metronidazole: adverse events

Answer 6

• **potentially carcinogenic=banned for use in food animals
• may be teratogenic: avoid in pregnant animals
• minimal GI upset, salivation, inappetence (better than most)
• *neurotoxicity: ataxia, seizures, lethargy
• drug interactions: caution if used with hepatic enzyme substrate drugs

Question 7

Nitrofurans: formulations

Answer 7

• Vet
  o Topical products
  o Solution for IU use in horses
• Human
  o Oral capsules (Nitrofurantoin): single-day UTI therapy

Question 8

Nitrofurans: mechanism

Answer 8

• Block bacterial pyruvate metabolism (energy production)

Question 9

**Nitrofurans: spectrum of activity

Answer 9

• Broad spectrum, but especially GRAM-NEGATIVE ENTERICS
• *can’t use for systemic infections
  o Reaching MIC in plasma requires doses that produce systemic TOXICITY

Question 10

Nitrofurans: resistance

Answer 10

• Does occur, but generally NO cross-resistance with other antimicrobial classes
• No usually included on C&S panel

Question 11

Nitrofurans: PK

Answer 11

• good oral absorption, topical absorption unknown
• wide distribution in body
• **excretion: RENAL (high concentrations in urine) (beta-lactams, TCs)
  o Low oral dose can be used, yet still get high [urine]

Question 12

Nitrofurans: adverse events

Answer 12

• Cardiomyopathy (ventricular dilation)
• Reproductive (endocrine) toxicity
• CARCINOGENICITY: banned for use in food animals

Question 13

Nitrofurazone: uses

Answer 13

• Found in wound creams and solutions
  o But they get used in dairy animals
• Topical and IU/intra-vaginal uses (horses)
• NOT for food-producing animals

Question 14

Nitrofurantoin: uses

Answer 14

• Has been used to treat E. coli/MDR UTIs in dogs and cats
• Appropriate doses not really known

Question 15

Rifamycins (Rifampin): formulations

Answer 15

• Human tablets

Question 16

Rifampin: mechanism

Answer 16

• Inhibits bacterial RNA polymerase
• Penetrates leukocytes, kills INTRACELLULAR pathogens
• Bacteriostatic, time-dependent antimicrobial activity

Question 17

Rifampin: spectrum

Answer 17

• Broad spectrum, but resistance is prevalent
• Mycobacterium (TB), Staph isolates, R. equi pneumonia in foals
• *resistance emerges rapidly: typically used along with ML or other antibiotics

Question 18

Rifampin: resistance

Answer 18

• A single AA change in bacterial RNA polymerase reduces BINDING

Question 19

Rifampin: PK (don’t really need to know)

Answer 19

• Good oral absorption in most species
• Wide distribution to variety of tissues
• Hepatic metabolism
• Biliary and renal excretion

Question 20

Rifampin: adverse events

Answer 20

• Red-tinged fluids: not a health concern
• Hepatic CYP and P-gp INDUCTION
  o Increase clearance of other drugs
• Teratogenic
• Blood dyscrasis (Rare): anemia and decreased platelets

Question 21

Glycopeptides (vancomycin): formulations

Answer 21

• All human
  o Oral tablets
  o Injectable solution
• DO NOT USE IN VET MED

Question 22

Glycopeptides (vancomycin): mechanism of action

Answer 22

• Inhibit peptidoglycan synthesis needed for cell wall

Question 23

Glycopeptides (vancomycin): spectrum of activity

Answer 23

• Gram + rods and cocci
  o Especially MRS, Enterococcus (but have other drugs we go to)
• Gram – bacteria=resistant

Question 24

Glycopeptides (vancomycin): resistance

Answer 24

• Major health concern
• *vancomycin-resistant Enterococci (VRE)

Question 25

Glycopeptides (vancomycin): PK

Answer 25

• Poor oral absorption, limited tissue distribution
• Excreted via glomerular filtration
  o Dose adjustments need for renal failure patients

Question 26

Glycopeptides (vancomycin): adverse events

Answer 26

• Very irritating upon injection: administer slowly IV
• Potentially nephrotoxic, ototoxic, allergenic

Question 27

Polymyxin B

Answer 27

• “cationic detergents”: bind to cell membrane and disrupt structure
• *Gram – bacteria only
• AE: wide range of toxicity with systemic administration (only used topically: Polysporin)

Question 28

Bacitracin

Answer 28

• Active against Gram + bacteria
• Similar mechanism to beta-lactams
• Found in topical formulations (BNP triple ointment)
• Also used in feed premixes in poultry and swine
  o Growth promoter, prevention of clostridial enteritis

Question 29

Fusidic acid

Answer 29

• Inhibits bacterial protein synthesis
• Isaderm germ (Fusidic acid + betamethasone)
  o Indicated from superficial pyoderma
  o Most Staph are susceptible (including MRSP)

Question 30

Mupirocin

Answer 30

• Blocks bacterial protein synthesis
• Rapidly metabolized after systemic administration
  o Only used topically, **typically for Staph infecitons
• good penetration into infected tissues
• only human formulations in Canada

Question 31

Linezolid

Answer 31

• NOT used in vet med

Question 32

Colistin

Answer 32

• NOT used in vet med
  -might see in swine practice (importing it in)